Renal disease is an important complication of diabetes mellitus. Studies evaluating renal changes in animals in which experimental diabetes was reversed by pancreatic islet isografting have shown that islet transplantation has beneficial effects upon experimental diabetic nephropathy. It is the purpose of the proposed research to further investigate the (1) Glomerular structural and functional abnormalities in streptozotocin-induced diabetes in the Lewis rat, and the effects of syngeneic islet transplantation on the prevention, amelioration or reversal of the diabetic renal lesions; (2) Tubular structural and functional studies in same or similary handled diabetic rats; (3) Role of high fat diets and hyperlipidemia on the induction or aggravation of diabetic renal lesions and their possible amelioration by hypolipemic diets or lipid-lowering agents; (4) Effects of islet transplantation late in the course of advanced diabetic nephropathy. Islets will be transplanted after varying degrees of diabetic renal insufficiency (with subtotal nephrectomy) in order to determine at what stage of progressive nephropathy islets can be expected to arrest the renal changes. Kidney and islets allografted at different times into immunomodified diabetic rats will be performed to obtain baseline data necessary before similar therapeutic procedures can be considered in patients. Sequential renal biopsies in all four studies will be examined by light, scanning and transmission electronmicroscopy. Electrondense tracers of different molecular sizes, light and electronmicroscopic study of the glomerular glycocalyx after colloidal iron staining, and evaluation of tubular as well as glomerular functions including characteristics of the proteinuria should permit a more precise evaluation of the renal abnormalities resulting from diabetes mellitus and the effect of islet transplantation on diabetic nephropathy.